This program is designed to determine the most effective way to implement, on a large scale, a preventive program of demonstrated feasibility for the control of the Lesch-Nyhan disease, a genetically-determined form of neurological disease and cerebral palsy. The components of the plan comprise a screening program in which the ratio of uric acid to creatinine is determined on urine specimens from various populations of handicapped individuals collected on small squares of filter paper on plastic dipsticks, dried and sent to our laboratory for automated analysis. All patients with Lesch-Nyhan disease have a substantially higher ratio of uric acid to creatinine than is found in the general population. Confirmatory tests using 24-hour urine excretion of uric acid and creatinine and blood samples for demonstrating the gross deficiency of the enzyme hypoxanthine guanine phosphoribosyltransferase in erythrocytes will be used to confirm the diagnosis in suspected cases first identified by the screening test. Since the disease is X-linked, subsequent components of the plan involve the detection of heterozygotes by demonstrating both normal and mutant cell populations in skin biopsies or hair follicles from the scalp in mothers, maternal grandmothers and great-grandmothers, when available. In this manner we will identify the generation in which the mutation has occurred, identify females in the child-bearing period in each generation who are heterozygotes and alert them to the need to have their pregnancies monitored by prenatal diagnosis, in order to avoid producing an affected male. Another component of the program will consist of encouraging the appropriate families to do genealogical research in order eventually to identify heterozygotes among more distant female relatives of the mother. Improved methods for heterozygote detection will also be developed.